Rajput A H, Gibb W R, Zhong X H, Shannak K S, Kish S, Chang L G, Hornykiewicz O
University of Saskatchewan, Saskatoon, Canada.
Ann Neurol. 1994 Apr;35(4):396-402. doi: 10.1002/ana.410350405.
We report the first neuropathological and neurochemical study of a patient with dopa-responsive dystonia. She had onset of foot dystonia at age 5 years and by age 8 years it was generalized with prominent right leg and arm involvement. On levodopa 750 mg daily she had complete symptomatic improvement that was sustained for 11 years until death. Pathological studies revealed normal numbers of hypopigmented substantia nigra neurons, normal tyrosine hydroxylase (TH) immunoreactivity and TH protein in the SN, no inclusion bodies or gliosis, and no evidence of a degenerative process in the striatum. Biochemical studies revealed reduced dopamine in the substantia nigra and striatum (8% in the putamen and 18% of control in the caudate) with a similar but not identical subregional distribution as in idiopathic Parkinson's disease. In the striatum, TH protein and TH activity was reduced, with the loss more pronounced in the putamen than the caudate. The GBR 12935 binding to DA transporter was normal in the caudate and at the lower end of the range of control values in the putamen. We conclude that disturbed dopamine synthetic capacity or a reduced arborization of striatal dopamine terminals may be the major disturbance in dopa-responsive dystonia.
我们报告了首例对一名多巴反应性肌张力障碍患者的神经病理学和神经化学研究。她5岁时开始出现足部肌张力障碍，8岁时病情全身性发作，右腿和右臂受累明显。每日服用750毫克左旋多巴后，她的症状完全改善，并持续了11年直至去世。病理研究显示，黑质中色素减退神经元数量正常，黑质中酪氨酸羟化酶（TH）免疫反应性和TH蛋白正常，无包涵体或胶质增生，纹状体也无退行性变过程的证据。生化研究显示，黑质和纹状体中的多巴胺减少（壳核中为对照值的8%，尾状核中为对照值的18%），其亚区域分布与特发性帕金森病相似但不完全相同。在纹状体中，TH蛋白和TH活性降低，壳核中的损失比尾状核更明显。尾状核中GBR 12935与多巴胺转运体的结合正常，壳核中的结合处于对照值范围的下限。我们得出结论，多巴胺合成能力紊乱或纹状体多巴胺终末分支减少可能是多巴反应性肌张力障碍的主要病变。
